研究报告

μ型阿片受体参与CFA大鼠慢性炎性痛的外周调控

何晓芬，蒋永亮，尹小虎，沈亚芳，方剑乔

(浙江中医药大学第三临床医学院，杭州310053)

【摘要】目的观察大鼠慢性炎性痛时背根神经节(dorsal root ganglion，DRG)μ型阿片受体(mu opioid receptor，MOR)表达的变化及炎症局部注射MOR激动剂和拮抗剂对痛阈的干预作用，探讨MOR在慢性炎性疼痛中的作用。 方法 足底注射弗氏完全佐剂(complete freund’s adjuvant，CFA)制备大鼠慢性炎性痛模型，采用免疫组化法检测DRG MOR阳性细胞的表达；经大鼠足跖背部分别注射MOR激动剂、拮抗剂，采用辐射热法检测给药前后大鼠痛阈的变化。 结果 足底注射CFA诱导出大鼠慢性炎性痛，在造模后第18天，痛阈依然低于正常对照组；免疫组化结果表明，与正常对照组相比，CFA大鼠DRG MOR阳性细胞表达增多(P < 0.01)；足跖背部注射MOR激动剂减轻CFA大鼠的疼痛，对正常大鼠痛阈无影响；足跖背部注射MOR拮抗剂加重CFA大鼠的疼痛，对正常大鼠痛阈无影响。 结论DRG神经元MOR在慢性炎性痛时表达上调，参与慢性炎性痛的外周调控，可能有助于防止慢性痛的进一步加重。

【关键词】外周；μ型阿片受体；慢性痛；炎症；

[基金项目]国家自然科学基金资助项目(81072855，81303039)；浙江省自然科学基金资助项目(LY12H27015，Z2100979)；国家中医药管理局重点学科(针灸学)建设经费资助(国中医药发[2009]30号)。

[作者简介]何晓芬(1986-)，女，助理研究员。研究方向；针刺镇痛与免疫调节的相关性研究。E-mail: zjhxf1986@163.com。

[通讯作者]方剑乔(1961-)，男，教授，博士生导师。研究方向：针刺镇痛与免疫调节的相关性研究。E-mail: fangjianqiao7532@163.com。

【中图分类号】R332【文献标识码】 A

doi:10.3969.j.issn.1671.7856. 2015.001.005

The involvement of mu opioid receptorin peripheral regulation of

chronic inflammatory pain induced by CFAin rats

HE Xiao-fen，JIANG Yong-liang，YIN Xiao-hu，SHEN Ya-fang，FANG Jian-qiao

(The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China)

Abstract【】ObjectiveTo investigate the change of mu opioid receptor (MOR) in dorsal root ganglion (DRG) in rat chronic inflammatory pain model and the effect of MOR agonist and antagonis tintraplantarly (i.pl.) injected on pain threshold, so as to determine the role of peripheral MOR in chron in inflammatory pain. Methods Chronicin flammatory pain model was established by i.pl. injection of CFA in rats. The expression of MOR in DRG was detected by immunohistochemistry. Pain threshold before and after i.pl. injection of MOR agonist and antagonist was measured by radiant heat method. ResultsRats suffered from an intraplantar injection of CFA developed chronic inflammatory pain,and the painthreshold still reduced on 18 day after CFA injection compared to that in the normal group. Immunohistochemistry staining revealed that compared with the normal group, the expression of MOR in DRG of CFA rats was increased (P<0.01). After the paw dorsal surface injection of MOR agonist, the pain threshold of CFA rats was increased, while that of normal rats exhibited no significant change. After the paw dorsal surface injection of MOR antagonist, the pain threshold of CFA rats was reduced, while that of normal rats had no significant change. Conclusion Under chronic inflammatory pain condition, DRG MOR expressionis enhanced, which participates in the regulation of chronic inflammatory pain, and may contribute to the prevention of further more serious pain.

【Key words】Periphery；Mu opioid receptor；Chronic pain；Inflammation

疼痛的慢性化是当前疼痛治疗的难点。传统的阿片类药物作为临床上最常用的镇痛药物之一[1-2]，主要通过激活中枢阿片受体发挥镇痛作用，但是除镇痛作用外，基于中枢神经系统的镇痛药物具有成瘾性、耐药性和呼吸抑制等中枢副作用[3-4]，因此，寻找能有效控制疼痛、减少毒副作用的新型镇痛药物已成为研究的热点。……